scholarly journals High expression of E-cadherin and Ki-67 associated with functional/dysfunctional phenotypes of tumor-infiltrating lymphocytes among Chinese patients with operable breast cancer

2018 ◽  
Vol 46 (12) ◽  
pp. 5219-5227 ◽  
Author(s):  
Ruibin Wang ◽  
Feng Shi ◽  
Lin Zhao ◽  
Yanjie Zhao ◽  
Guangjiang Wu ◽  
...  

Objective Breast cancer has become the most common cancer in women in China, and the clinicopathological features differ from those in Western patients. This study was performed to investigate the distribution of programmed cell death protein 1 (PD-1)+/PD-1− tumor-infiltrating lymphocytes (TILs) and its association with clinicopathological features among Chinese patients with breast cancer. Methods In total, 133 consecutive patients with primary breast cancer were recruited into this cross-sectional study from 2012 to 2013. TILs were measured by cell counts under high-power fields (HPFs). Immunohistochemistry was used to detect PD-1 expression on tumor-infiltrating lymphocytes in the microenvironment. Results The median cell counts of the overall TILs, PD-1+ TILs, and PD-1− TILs were 80, 18, and 55/HPF, respectively. The number of PD-1− TILs was significantly lower in older than younger patients (50 vs. 60/HPF). Patients with positive E-cadherin expression had more PD-1− TILs than patients with negative E-cadherin expression (57 vs. 27/HPF). The Ki-67 index was positively correlated with the cell counts of PD-1+ TILs, and the correlation coefficient was 0.29. Conclusions PD-1 expression on TILs had different clinicopathological features in Chinese patients with breast cancer. E-Cadherin expression was associated with PD-1− TILs; however, Ki-67 expression was associated with PD-1+ TILs.

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yan-Jie Zhao ◽  
Jian Zhang ◽  
Feng Shi ◽  
Zhi-Ping Hu ◽  
Jiang-Ping Wu ◽  
...  

Objective. This study aimed to investigate the correlation of CD4+/PD-1+ or CD4+/PD-1− tumor-infiltrating lymphocytes with pathological characteristics in breast cancer patients. Methods. A cross-sectional study consecutively recruited 133 patients with invasive ductal breast cancer. The expression of CD4, programmed cell death protein 1 (PD-1), CK7, CK20, E-cadherin, or Ki-67 was detected by immunohistochemistry. The associations between CD4+/PD-1+ or CD4+/PD-1− tumor-infiltrating lymphocytes and pathological characteristics were evaluated. Results. Elderly patients intended to have a lower level of CD4+/PD-1− tumor-infiltrating lymphocytes (p<0.05). Patients with positive E-cadherin expression had higher median cell counts of CD4+/PD-1− tumor-infiltrating lymphocytes than patients with negative E-cadherin expression (30/HPF versus 10/HPF, p<0.05). Counts of CD4+/PD-1+ tumor-infiltrating lymphocytes had a significant correlation with Ki-67 index that the correlation coefficient was 0.29 (p=0.001). Positive CK20 expression was related to a higher level of CD4+/PD-1− tumor-infiltrating lymphocytes than negative CK20 expression (73/HPF versus 30/HPF, p<0.05). Conclusion. CD4+/PD-1+ or CD4+/PD-1− tumor-infiltrating lymphocytes showed diverse association with pathological features of breast cancer. CD4+/PD-1+ tumor-infiltrating lymphocytes had a significant relationship with Ki-67 expression whereas CD4+/PD-1− tumor-infiltrating lymphocytes had a significant relationship with E-cadherin expression. Further studies are warranted to explore the immunomodulatory effects of phenotypes of CD4+ T cell subsets in breast cancer.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Qingkun Song ◽  
Feng Shi ◽  
Maya Adair ◽  
Hong Chang ◽  
Xiudong Guan ◽  
...  

Objective. This study is aimed at investigating the association of exhausted CD8+ tumor-infiltrating lymphocytes with clinic-pathological factors. Methods. 133 patients diagnosed with primary invasive ductal breast cancer were recruited into the cross-sectional study consecutively. Immunohistochemistry was used to detect biomarker expression on formalin-fixed and paraffin-embedded sections. Double staining of CD8 and PD-1 was conducted on lymphocytes. Results. The proportion of CD8+/PD-1- TILs was 16% among patients with axillary lymph node metastasis, significantly lower than those without metastasis (24%). The expression of CK7, CK20, or Ki-67 was not related with the proportion of phenotypes of CD8/PD-1 TILs. Younger patients had more cell counts of CD8+/PD-1- TILs than elderly patients (18/HPF vs. 9/HPF, p<0.05). Patients with axillary lymph node metastasis had less CD8+/PD-1- TILs than those without metastasis (11/HPF vs. 27/HPF, p<0.05). Median counts of CD8+/PD-1- TILs among patients with CK20 and E-Cad expression were 33/HPF and 14/HPF, significantly higher than those among patients with negative CK20 (16/HPF) and E-Cad expression (6/HPF). Ki-67 index had a significant correlation with cell counts of CD8+/PD-1+ TILs and CD8+/PD-1- TILs, and the correlation coefficients were 0.19 and 0.21 (p<0.05), respectively. Conclusion. The proportion of CD8+/PD-1- TILs was related with metastatic status of the axillary lymph node but cell counts of CD8+/PD-1- TILs were related with metastatic status of the axillary lymph node and expression of CK7, CK20, E-Cad, and Ki-67. Absolute cell counts, not proportion of CD8/PD-1 TILs, were more likely to distinguish clinic and pathologic characteristics of breast cancer.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Farzin Negahbani ◽  
Rasool Sabzi ◽  
Bita Pakniyat Jahromi ◽  
Dena Firouzabadi ◽  
Fateme Movahedi ◽  
...  

AbstractThe nuclear protein Ki-67 and Tumor infiltrating lymphocytes (TILs) have been introduced as prognostic factors in predicting both tumor progression and probable response to chemotherapy. The value of Ki-67 index and TILs in approach to heterogeneous tumors such as Breast cancer (BC) that is the most common cancer in women worldwide, has been highlighted in literature. Considering that estimation of both factors are dependent on professional pathologists’ observation and inter-individual variations may also exist, automated methods using machine learning, specifically approaches based on deep learning, have attracted attention. Yet, deep learning methods need considerable annotated data. In the absence of publicly available benchmarks for BC Ki-67 cell detection and further annotated classification of cells, In this study we propose SHIDC-BC-Ki-67 as a dataset for the aforementioned purpose. We also introduce a novel pipeline and backend, for estimation of Ki-67 expression and simultaneous determination of intratumoral TILs score in breast cancer cells. Further, we show that despite the challenges that our proposed model has encountered, our proposed backend, PathoNet, outperforms the state of the art methods proposed to date with regard to harmonic mean measure acquired. Dataset is publicly available in http://shiraz-hidc.com and all experiment codes are published in https://github.com/SHIDCenter/PathoNet.


2020 ◽  
Vol 21 (4) ◽  
pp. 1135-1142
Author(s):  
Thuan Dang Cong ◽  
Tung Nguyen Thanh ◽  
Quynh Anh Nguyen Phan ◽  
Ai Phuong Hoang Thi ◽  
Bao Song Nguyen Tran ◽  
...  

2020 ◽  
Author(s):  
Romana Idress ◽  
Faiza Rasheed ◽  
Jamshid Abdul-Ghafar ◽  
Abida Sattar ◽  
Zubair Ahmad

Abstract Background The debate whether breast cancer in women under 40 years of age is distinct from breast cancer in women above 40 is still inconclusive with various published studies providing conflicting evidence. The majority of studies however suggest that breast cancer in younger women (< 40) is more aggressive with worse clinicopathological features. However, the issue is by no means settled and a number of studies are still going on. Our objective was to analyze different clinicopathological variables and determine whether statistically significant differences are present between those under 40 and those above 40 years of age. The present paper contributes to this debate by reporting our findings. Methods Descriptive cross sectional study of 482 breast cancer cases reported between January and December 31, 2016 which included 380 patients (above 40 years of age) and 102 (under 40 years of age). Variables included grade, stage, axillary lymph node metastases, lymphovascular invasion and molecular groups. p-value less than 0.05 was taken as significant. Results Over 21% patients were younger than 40 years. Differences in histologic grade, stages of T1, T2, and T4, Estrogen Receptor (ER) and Progesterone Receptor (PR) status, Her2neu status, triple negativity and molecular groups between patients younger than 40 years and those older than 40 years were statistically insignificant. Differences in stage T3, axillary metastases and lymphovascular invasion were statistically significant. Conclusion Statistically significant differences were noted in some clinicopathological variables. Majority of variables indicating more aggressive disease were seen in patients older than 40 years of age. Additional studies with larger number of patients under 40 years of age are required to resolve the issue conclusively so that young women with breast cancer are not treated too aggressively unless there is unequivocal statistical evidence that breast cancer is more aggressive in patients under 40 years of age.


2021 ◽  
Vol 11 (15) ◽  
pp. 6788
Author(s):  
Giuseppe Angelico ◽  
Giuseppe Broggi ◽  
Rosario Caltabiano ◽  
Angela Santoro ◽  
Saveria Spadola ◽  
...  

Background: In the present study, we evaluated the prognostic value of TILs as well their relation with clinicopathological factors in patients affected by HER-2 positive breast cancer. Methods: We evaluated 47 patients with a histologically confirmed diagnosis of invasive breast carcinoma showing an immunohistochemically confirmed (score 3+) amplification of the c-erbB-2 gene for the presence of TILs and categorized in three predefined groups of low (0–10% immune cells in stromal tissue within the tumor), intermediate (11–40%), and high TILs (>40%). Results: Low, intermediate and high TILs were found in 17/47 (36%), 23/47 (49%) and 7/47(15%) cases, respectively. It was found that 6/47 cases treated with adjuvant chemotherapy plus trastuzumab underwent progression of the disease; none of these cases exhibited high TILs. It was found that 12/47 patients with a prognostically unfavorable stage of III and IV showed low and intermediate levels of TILs, while high TILs were never observed. A significant association between intermediate/high-levels of TILs, elevated KI 67 index and hormone receptors nuclear staining was observed. High concordance in TILs distribution was observed between preoperative breast biopsies and surgical samples. Conclusions: We observed a positive correlation between the TILs and the response to both adjuvant and neoadjuvant treatments in HER-2 positive BC. High TILs were also related to increased KI-67 index and to the expression of hormone receptors.


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